Alcohol-induced chronic gastritis is characterized by mucosal cell injury and infiltration of leukocytes. As with alcoholic liver cirrhosis, not all alcoholics develop chronic gastritis. Unlike alcoholic cirrhosis, however, little is known about immunologic mechanisms involved in the pathogenesis of alcoholic gastritis and the role of gastric tissue in this process. Recent studies of liver cirrhosis indicated: 1) the release of leukocyte chemotactic factor (LCF) from cultured hepatocytes exposed to ethanol, a mechanism by which circulating leukocytes could be recruited to liver tissue, and 2) the detection of high levels of chemotactic factor inhibitors (CFI) in serum of alcoholic patients, a mechanism which may be responsible for the suppression of inflammation (i.e., chemotaxis) and increase susceptibility to infection in these patients. Cells releasing these inhibitors have not yet been identified. Since gastric tissues are the first to be exposed to ingested ethanol and are exposed to the highest concentrations for a length of time (i.e., minutes), we began evaluating their capability to release CFI. Our preliminary results indicated the release of high levels of CFI from ethanol- treated gastric mucosa and serosa. We now propose to further establish this phenomenon and evaluate a mechanism by which CFI exhibit their action. Our hypothesis is that gastric tissue exposed to ethanol releases CFI which reduces leukocyte chemotaxis by deactivating chemotactic factors rather than acting directly on leukocytes. To test this hypothesis, isolated full-thickness segments of rabbit stomachs (antrum and fundus) will be placed in Ussing chambers and treated with ethanol or Ringer solution. Ethanol will be tested at high (20%, 50% and 100% v/v for 5, 10 and 20 min) and low (0.01% and 0.001% v/v for 60, 90 and 120 min) concentrations. Following incubation at 37oC, supernatants will be collected and evaluated for the presence and potency of CFI by incubation (37 degrees C for 30 min) with individual chemotactic factors (C5 fragment, bacterial chemotactic factors and gastric derived chemotactic factors). Residual chemotactic activity will be assayed using modified Boyden chambers and rabbit peritoneal neutrophils as indicator cells. Results of these studies will provide insights on the role of gastric tissue (through the release of CFI) on the regulation of host immunity following alcohol consumption. Future isolation and characterization of CFI released from ethanol treated gastric tissue will identify immunosuppressive factors which may play an important role in the increased risk for infection in alcoholic patients.